Bradley J. Monk, MD, FACS, FACOG: We have said that neoadjuvant therapy is common. So, if you wanted to use bevacizumab (Avastin) in the neoadjuvant setting, how do you do that?

Matthew Powell, MD: Well, there is a recent abstract that was presented at the ASCO Annual Meeting last year. It looked at giving bevacizumab with up-front neoadjuvant chemotherapy. The first 3 cycles were with bevacizumab and cytotoxic chemotherapy. At the cycle right before surgery, their interval cytoreduction, they held the bevacizumab and operated on these patients. Results showed a little bit of what they called “improved surgical outcomes,” where they’re more likely to get the disease to go away. Really, there was no difference in progression-free survival and immature overall survival, at this point. I think safety was shown. That’s about all I could say, at this point.

Bradley J. Monk, MD, FACS, FACOG: So, we have some controversy here. Generally, when we do neoadjuvant, we do 3 cycles. If you want to give 3 cycles of bevacizumab, since you don’t give bevacizumab before surgery, the 3 cycles turns into 4. You get 3 of chemotherapy of bevacizumab and then the fourth. Many times, we thought we weren’t prepared to give it on the first cycle. I think that trial shows that you can give bevacizumab right out of the gate. There was controversy that said that if the cancer was on the bowel, we might cause a gastrointestinal perforation. That appears to have not been borne out in this and other clinical trials. So, I don’t think I know whether to give 4 cycles or 3 cycles, and just give 2 cycles of bevacizumab or just to give bevacizumab after the neoadjuvant surgery, which is certainly another option.

Ursula Matulonis, MD: Do you think that the trial—the small phase II randomized trial that has not been published yet—gives you, as a surgeon, enough justification to use bevacizumab in the first cycle?

Matthew Powell, MD: I don’t think bevacizumab, in the first cycle, is enough of a problem, in my mind. Our recurrent-disease patients are getting bevacizumab, in their first cycle, all the time.

David O’Malley, MD: So, where is this or was this drug used the most? In metastatic colorectal, stage 4, parenchymal metastases.

They’ve clearly shown that they can perform a liver resection after bevacizumab. They give at least 6 weeks, and up to 12 weeks. So, we published a phase I trial that also looked at this question of bevacizumab in the up-front setting. Again, it’s a phase I trial. It’s a small trial, but we did the exact same thing. We held the bevacizumab. You have to hold the bevacizumab for at least 6 weeks, for the long half-life. I would even encourage clinicians to hold for 8 or more weeks to make sure that’s out. In regard to the question about why bowel perforations are down, we’re a lot smarter about giving it, right? When we were giving it to everybody, we perforated a lot of bowels. The number was as high as 11% in one publication.

Transcript Edited for Clarity

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Transcript:

Bradley J. Monk, MD, FACS, FACOG: We have said that neoadjuvant therapy is common. So, if you wanted to use bevacizumab (Avastin) in the neoadjuvant setting, how do you do that?

Matthew Powell, MD: Well, there is a recent abstract that was presented at the ASCO Annual Meeting last year. It looked at giving bevacizumab with up-front neoadjuvant chemotherapy. The first 3 cycles were with bevacizumab and cytotoxic chemotherapy. At the cycle right before surgery, their interval cytoreduction, they held the bevacizumab and operated on these patients. Results showed a little bit of what they called “improved surgical outcomes,” where they’re more likely to get the disease to go away. Really, there was no difference in progression-free survival and immature overall survival, at this point. I think safety was shown. That’s about all I could say, at this point.

Bradley J. Monk, MD, FACS, FACOG: So, we have some controversy here. Generally, when we do neoadjuvant, we do 3 cycles. If you want to give 3 cycles of bevacizumab, since you don’t give bevacizumab before surgery, the 3 cycles turns into 4. You get 3 of chemotherapy of bevacizumab and then the fourth. Many times, we thought we weren’t prepared to give it on the first cycle. I think that trial shows that you can give bevacizumab right out of the gate. There was controversy that said that if the cancer was on the bowel, we might cause a gastrointestinal perforation. That appears to have not been borne out in this and other clinical trials. So, I don’t think I know whether to give 4 cycles or 3 cycles, and just give 2 cycles of bevacizumab or just to give bevacizumab after the neoadjuvant surgery, which is certainly another option.

Ursula Matulonis, MD: Do you think that the trial—the small phase II randomized trial that has not been published yet—gives you, as a surgeon, enough justification to use bevacizumab in the first cycle?

Matthew Powell, MD: I don’t think bevacizumab, in the first cycle, is enough of a problem, in my mind. Our recurrent-disease patients are getting bevacizumab, in their first cycle, all the time.

David O’Malley, MD: So, where is this or was this drug used the most? In metastatic colorectal, stage 4, parenchymal metastases.

They’ve clearly shown that they can perform a liver resection after bevacizumab. They give at least 6 weeks, and up to 12 weeks. So, we published a phase I trial that also looked at this question of bevacizumab in the up-front setting. Again, it’s a phase I trial. It’s a small trial, but we did the exact same thing. We held the bevacizumab. You have to hold the bevacizumab for at least 6 weeks, for the long half-life. I would even encourage clinicians to hold for 8 or more weeks to make sure that’s out. In regard to the question about why bowel perforations are down, we’re a lot smarter about giving it, right? When we were giving it to everybody, we perforated a lot of bowels. The number was as high as 11% in one publication.